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PDGF-induced fibroblast growth requires monounsaturated fatty acid production by stearoyl-CoA desaturase.

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Coomans de Brachène, Alexandra Dif, Nicolas de Rocca Serra, Audrey Bonnineau, Chloé Velghe, Amélie I Larondelle, Yvan [UCL] Tyteca, Donatienne [UCL] Demoulin, Jean-Baptiste

Stearoyl-coenzyme A desaturase (SCD) catalyzes the Δ9-cis desaturation of saturated fatty acids (SFA) to generate monounsaturated fatty acids (MUFA). This enzyme is highly up-regulated by platelet-derived growth factor (PDGF) in human fibroblasts. Accordingly, the analysis of cellular fatty acids by gas chromatography showed that PDGF significantly increased the proportion of MUFA, particularly palmitoleate, in cellular lipids. To further analyze the role of SCD in fibroblasts, we used small hairpin RNA targeting SCD (shSCD), which decreased the MUFA content. SCD down-regulation blunted the proliferation of fibroblasts in response to PDGF. This was confirmed using a pharmacological inhibitor of SCD. In addition, proliferation was blocked by palmitate and stearate (two SCD substrates) but not by palmitoleate and oleate (two SCD products). In the presence of an equal amount of oleate, palmitate had no effect on cell proliferation. SCD inhibition or down-regulation did not decrease PDGF receptor activity or signaling. However, by measuring plasma membrane lipid lateral diffusion by fluorescence recovery after photobleaching, we showed that the modulation of the MUFA/SFA ratio by PDGF and SCD inhibitor was related to modifications of membrane fluidity. Altogether, our data suggest that SCD is required for the response of normal fibroblasts to growth factors.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès libre
Publication date 2017
Language Anglais
Journal information "F E B S Open Bio" - Vol. 7, no. 3, p. 414-423 (2017)
Peer reviewed yes
Publisher Elsevier BV
issn 2211-5463
e-issn 2211-5463
Publication status Publié
Affiliations UCL - SSS/DDUV - Institut de Duve
UCL - SSH/IACS - Institute of Analysis of Change in Contemporary and Historical Societies
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Bibliographic reference Coomans de Brachène, Alexandra ; Dif, Nicolas ; de Rocca Serra, Audrey ; Bonnineau, Chloé ; Velghe, Amélie I ; et. al. PDGF-induced fibroblast growth requires monounsaturated fatty acid production by stearoyl-CoA desaturase.. In: F E B S Open Bio, Vol. 7, no. 3, p. 414-423 (2017)
Permanent URL http://hdl.handle.net/2078.1/183661